Metabolic changes observed with proton-magnetic-resonance-spectroscopy (1H-MRS) often augment the highly sensitive but not specific MRI. Indeed, at 1.5 Tesla, 1H-MRS has so far linked anatomy from MRI with underlying metabolism in cancer, Alzheimer's and Parkinson's diseases, MS, HIV, epilepsy, stroke trauma and other neurological and psychiatric disorders. It was anticipated, therefore, that high, B0 e3 T, magnetic-fields would provide 1H-MRS a much needed boost in sensitivity, spectral and spatial resolution. That unfortunately, did not happen despite their proliferation in number, :300 installed, and field strength, up to 9.4 T. Translation of the most useful two and three dimensional (2D, 3D) 1H-MRS techniques to high-fields has been stymied by: (i) High radio-frequency (B1) power requirements and heat deposition;(ii) short T2s, reducing the signal-to- noise-ratio (SNR) gain;(iii) chemical shift displacement errors;and (iv) lack of software to evaluate and display the large data sets. Consequently, efficient, reliable 3D multivoxel techniques are not offered by instrument manufacturers, who traditionally shift this onus onto publicly-funded academic research. The long term goal of this competing continuation, therefore, is to develop methods to address issues i - iv to perform 3D 1H-MRS at higher B0s, and realize the advantages for clinical research. Our response to these problems is to extend to 3 and 7 T our successful hybrid techniques. Specific Aim 1 is to exploit the shorter T2s to enhance the SNR and acquisition efficiency of 3D coverage by optimal interleaving across the volume-of-interest (VOI), multiple slabs of several slices each. Specific Aim 2 is to overcome the declining B1 fields per watt RF power with shifted-Hadamard pulses that need the B1 of just one slice to sequentially excite several. This will lower the peak and deposited power under very strong selective gradients and reduce the chemical shift displacement. Specific Aim 3, is to recover the SNR lost to shorter T2s at high B0s with non-echo sequences using 3D transverse and longitudinal-Hadamard encoding to define the VOI. Finally, Specific Aim 4 is to develop new post-processing methods to detect and visualize relationships between different metabolites'spatial distributions to simplify the daunting amounts of 3D 1H MRS data.PROJECT NARRATIVE This project will lead to increases in the amount of human brain volume covered in an exam, improve the localization accuracy as well as spatial and spectral resolution and shorten the acquisition time for proton spectroscopy at higher magnetic fields. These capabilities will enhance studies of the underlying metabolism of devastating (but frequently MRI-invisible or of non-specific finding) neurological diseases in the human brain and spine and may also improve our capability to monitor the effectiveness of their treatment(s).